OBJECTIVE The increase in oxidative stress following neonatal hypoxia-reoxygenation can be related to subsequent cardiovascular deficits. We compared the acute systemic, pulmonary and regional hemodynamic recovery in hypoxic newborn pigs reoxygenated by low (18%) or high (100%) concentration of oxygen with that by 21% oxygen. METHODS Pigs (1-3 days, 1.5-2.5 kg) were acutely instrumented to continuously measure pulmonary artery flow (surrogate for cardiac index), mean and pulmonary artery pressures, common carotid, superior mesenteric and renal artery flow indices. After 1h of normocapnic alveolar hypoxia (8-10% oxygen), animals were randomized to receive 18%, 21% or 100% oxygen for 1h then 21% oxygen for 3 h (n=7 per group). Sham-operated pigs (n=6) had no hypoxia-reoxygenation. RESULTS Severe hypoxia caused significant compromises in systemic and regional hemodynamics and oxygen delivery (vs. shams). Despite reoxygenation, mean arterial pressure remained significantly lower than that of shams with no difference among hypoxic-reoxygenated groups. There was an oxygen-dependent recovery of pulmonary artery pressure. Cardiac index improved with reoxygenation but deteriorated over time in the 100% group. Both 18% and 100% groups had lower systemic oxygen delivery. Regional flows and oxygen delivery in all hypoxic-reoxygenated piglets were similarly reduced in all groups. CONCLUSIONS In this swine model of neonatal hypoxia-reoxygenation, resuscitation with 18% and 100% oxygen results in differential compromises in systemic and pulmonary circulations when compared with 21% oxygen.